Work during the fiscal year extended our prior research on the function of the basal ganglia in animal models of neurologic disorders. Our work was the first to demonstrate that there is an abnormal coupling of Drd1a dopamine receptors to activation of Extracellular Receptor Kinase (ERK1/2) in an animal model of Parkinson's Disease (Gerfen et al., 2002). During the past year we demonstrated that there are distinct forms of Drd1a-mediated activation of ERK signaling in the dorsal striatum and the nucleus accumbens (Gerfen et al., 2008). Using Drd1a- and DARPP32-deficient transgenic mice we show that in the dopamine intact accumbens, psychostimulants activate ERK1/2 via a Drd1a- and DARPP32-dependent mechanism. This mechanism is activated in the dorsal striatum only following dopamine depletion as occurs in Parkinson's Disease. [unreadable] [unreadable] Further work on the cellular mechanisms underlying neurologic and pscyhiatric disorders is limited by the fact that neurons throughout the brain utilize common mechanisms for critical functions such as synaptic plasticity, whereas specific neural systems are affected in different disorders. A large part of the Laboratory is now working with the Gene Expression Nervous System Atlas (GENSAT) project ( funded by NINDS and NIMH ) to produce transgenic mice with Cre-recombinase under the regulation of promoters to drive expression in specific neuron populations. Our part of this work is to characterize the expression of Cre in the brains of such transgenic lines and to provide such lines to the Mutant Mouse Regional Resource Center (MMRRC) for distribution to the research community. In the past year we characterized 14 Cre driver lines and are in the process of characterizing 25-50 lines for the current year ( Gong et al., 2007)